Estrogen induces repression of the breast cancer and salivary gland expression gene in an estrogen receptor α-dependent manner

Estrogen induces repression of the breast cancer and salivary gland expression gene in an estrogen receptor α-dependent manner
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DOI:
10.1158/0008-5472.can-07-5647
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发表时间:
2008-01-01
期刊:
影响因子:
11.2
通讯作者:
Denger, Stefanie
Denger, Stefanie
中科院分区:
医学1区
文献类型:
--
作者:
Bretschneider, Nancy;Brand, Heike;Denger, Stefanie

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本研究的重点是雌激素调节的乳腺癌和唾液腺表达(BASE)基因的表达和调节,该基因可能作为乳腺癌标志物。在 MCF7 细胞中,BASE 以雌激素受体 α (ER α) 依赖性方式被雌激素抑制。对 BASE 基因的启动子分析发现了一个 2-kb 上游增强子,该增强子包含 ER α 和 FoxA1 的结合位点。染色质免疫沉淀分析显示 ER α 和 FoxA1 均募集至该区域。此外,突变研究和敲低实验表明 FoxA1 介导的基因表达和 ER α 依赖性基因调控之间存在明显的分离。此外,我们还提供有关人类乳腺肿瘤样本中 BASE 表达的信息。
The focus of this study is on the expression and regulation of the estrogen-regulated breast cancer and salivary gland expression (BASE) gene that may function as a breast cancer marker. In MCF7 cells, BASE is repressed by estrogen in an estrogen receptor alpha (ER alpha)-dependent manner. Promoter analysis of the BASE gene led to the identification of a 2-kb upstream enhancer that harbors binding sites for ER alpha and FoxA1. The recruitment of both ER alpha and FoxA1 to this region was shown by chromatin immunoprecipitation analysis. Furthermore, mutation studies and knockdown experiments show a clear separation between gene expression mediated by FoxA1 and ER alpha-dependent gene regulation. Additionally, we provide information on BASE expression in human breast tumor samples.